Each year in the U.S. approximately 33,000 individuals will be newly diagnosed with leukemia and 23,300 will die from the disease. Little is known about the etiology of adult leukemia. Minnesota has the highest incidence rate of adult leukemia in the continental United States. In this proposed population-based case control study in Minnesota, we will systematically examine environmental and genetic factors that may contribute to adult leukemia. Due to a concurrent study of chronic lymphocytic leukemia (CLL) in southern Minnesota, we will focus this study on myeloid leukemia including acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). A total of 711 cases of incident adult myeloid leukemia and 711 frequency matched population controls will be enrolled. Questionnaire data through telephone interviews and mouthwash samples for genotyping will be obtained. We will evaluate risk factors for myeloid leukemia combined, separately for the two major groups enrolled and by morphologically and cytogenetically defined subgroups if feasible. In addition to evaluating risk factors such as cigarette smoking, occupational exposures to benzene and ionizing radiation, and prior chemotherapy treatments, we will investigate a) the role of non-steroidal anti-inflammatory drugs (NSAIDs) in risk of leukemia b) farming practices and related exposures in association with adult leukemia, c) obesity as a risk factor, and d) the role of genetic susceptibility genes including PON1, CYPs (2C9,3A4,2E1,2D6), GSTs (M1/T1), UGT1A6, PLA2, ODC, MDR1, MPO, NQ01, LEPR, and LEP. Based on our preliminary data, we hypothesize that frequent aspirin use (but not non-aspirin NSAID use) will be associated with a decreased risk of adult myeloid leukemia, particularly, AML. We also hypothesize that livestock farmers using animal insecticides will be at an increased risk (particularly, CML). We also expect that obesity will be more frequent among cases than controls. Further we hypothesize that genetic differences in the ability to metabolize NSAIDs, detoxify environmental toxins (including pesiticides, cigarette smoke) and metabolize leptin contributes to risk. Finally, we hypothesize that unfavorable genotypes, in combination with specific exposures, increase the risk of adult myeloid leukemia. The significance of this proposal, specifically with respect-to the identification of possible prevention strategies for adult AML, has important public health implications.